This invention pertains to the production of propiophenone by a vapor-phase, cross-decarboxylation process and more particularly to the suppression of by-product formation.
Propiophenone is used as a starting material in pharmaceutical applications particularly for the manufacture of dextropropoxyphene or alpha-d-4-dimethylamino-3-methyl-1,2-diphenyl-2-butanol propionate. Propiophenone can be produced by a Friedel-Crafts reaction of benzene and propionic acid, propionic anhydride or propionyl chloride catalyzed by Lewis acids. Although Friedel-Crafts processes produce no significant amounts of aromatic ketone by-products, such processes suffer from very high costs involved in corrosion of production facilities and waste disposal required for environmental protection.
An attractive alternative synthesis of propiophenone and other specialty ketones utilizes a vapor-phase cross-decarboxylation process. In the case of propiophenone, benzoic acid is reacted with propionic acid at high temperatures over a catalyst. Propiophenone, diethyl ketone, carbon dioxide, and water are the major products. Numerous by-products are also formed in small amounts, including other dialkyl ketones, other phenylalkyl ketones and biphenol. One of the by-products produced in the vapor-phase process is isobutyrophenone. Depending upon the process conditions used, isobutyrophenone production may equal 10 percent or more of the propiophenone production. Separation of isobutyrophenone from propiophenone is impossible using conventional distillation techniques, inasmuch as the boiling points of these two compounds are within 1.degree. C. of each other. Other separation techniques, such as fractional crystallization or extractive distillation are costly and have not been perfected for this particular separation problem.
Dextropropoxyphene is used medically as an analgesic. Drug dependence associated with its use has been found to be uncommon. Unfortunately, its isomer prepared from isobutyrophenone rather than propiophenone has been found to be an addictive narcotic. Therefore, it is essential that propiophenone used for the preparation of dextropropoxyphene be of high purity such that the isobutyrophenone content shall be as low as possible.
It is therefore an object of this invention to provide a vapor-phase, cross-decarboxylation synthesis for the preparation of alkyl aryl ketones with a minimum of by-products.
It is a specific object of this invention to prepare propiophenone by the catalytic vapor-phase cross-decarboxylation of benzoic acid with propionic acid, in which the content of the by-product isobutyrophenone is held to a minimum.